Oncotarget

Research Papers:

Clinical application of targeted next-generation sequencing for colorectal cancer patients: a multicentric Belgian experience

Nicky D’Haene _, Quitterie Fontanges, Nancy De Nève, Oriane Blanchard, Barbara Melendez, Monique Delos, Marie-Françoise Dehou, Calliope Maris, Nathalie Nagy, Emmanuel Rousseau, Josse Vandenhove, André Gilles, Carine De Prez, Laurine Verset, Marie-Paule Van Craynest, Pieter Demetter, Jean-Luc Van Laethem, Isabelle Salmon and Marie Le Mercier

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Oncotarget. 2018; 9:20761-20768. https://doi.org/10.18632/oncotarget.25099

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Abstract

Nicky D’Haene1, Quitterie Fontanges1, Nancy De Nève1, Oriane Blanchard1, Barbara Melendez1, Monique Delos2, Marie-Françoise Dehou3, Calliope Maris1,4, Nathalie Nagy5, Emmanuel Rousseau6, Josse Vandenhove7, André Gilles8, Carine De Prez9, Laurine Verset1,10, Marie-Paule Van Craynest11, Pieter Demetter1, Jean-Luc Van Laethem12, Isabelle Salmon1 and Marie Le Mercier1

1Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium

2Department of Pathology, CHU UCL Namur, Yvoir, Belgium

3CMP Pathology Laboratory, Brussels, Belgium

4Department of Pathology, Braine l´Alleud Waterloo Hospital, Braine l´Alleud, Belgium

5Department of Pathology, Charleroi University Hospital, Charleroi, Belgium

6Department of Pathology, Mouscron Hospital, Mouscron, Belgium

7Department of Pathology, Sint Maria Hospital, Halle, Belgium

8Department of Pathology, EPICURA Hospital, Frameries, Belgium

9Department of Pathology, Brugmann University Hospital, Brussels, Belgium

10CurePath, Jumet, Belgium

11New LabPatho, Braine l´Alleud, Belgium

12Department of Oncology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium

Correspondence to:

Nicky D’Haene, email: nicky.d.haene@erasme.ulb.ac.be

Keywords: colorectal cancer; next-generation sequencing

Abbreviations: CRC: Colorectal Cancer; NGS: Next-generation sequencing; FFPE: formalin-fixed paraffin-embedded; TAT: turnaround time

Received: December 12, 2017     Accepted: March 17, 2018     Published: April 17, 2018

ABSTRACT

International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions.

The Ion Torrent AmpliSeq colon/lung cancer panel, which allows mutation detection in 22 cancer-related genes, was prospectively used in clinical practice (BELAC ISO 15189 accredited method). The DNA of 741 formalin-fixed paraffin-embedded CRC tissues, including primary tumors and metastasis, was obtained from 14 different Belgian institutions and subjected to targeted NGS.

Of the tumors tested, 98% (727) were successfully sequenced and 89% (650) harbored at least one mutation. KRAS, BRAF and NRAS mutations were found in 335 (46%), 78 (11%) and 32 (4%) samples, respectively. These mutation frequencies were consistent with those reported in public databases. Moreover, mutations and amplifications in potentially actionable genes were identified in 464 samples (64%), including mutations in PIK3CA (14%), ERBB2 (0.4%), AKT1 (0.6%), and MAP2K1 (0.1%), as well as amplifications of ERBB2 (0.3%) and EGFR (0.3%). The median turnaround time between reception of the sample in the laboratory and report release was 8 calendar days.

Overall, the AmpliSeq colon/lung cancer panel was successfully applied in daily practice and provided reliable clinically relevant information for CRC patients.


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